P
US9329185B2ActiveUtilityPatentIndex 39

Sulfonate compounds

Assignee: UNIV MASSACHUSETTSPriority: Mar 15, 2013Filed: Mar 10, 2014Granted: May 3, 2016
Est. expiryMar 15, 2033(~6.7 yrs left)· nominal 20-yr term from priority
Inventors:MILLER STEPHEN CPAUFF STEVEN MCHOI ADAM
G01N 33/582C07C 1/00
39
PatentIndex Score
0
Cited by
10
References
24
Claims

Abstract

This disclosure relates to compounds containing a fluorophore covalently bonded to at least one protected sulfonate group of formula (I): in which X and R 2 -R 5 are defined in the specification. This disclosure also relates to use of these compounds as dyes in an imaging methods, as well as intermediates that can be used to prepare these compounds.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       1. A compound, comprising:
 a fluorophore covalently bonded to at least one protected sulfonate group of formula (I): 
 
       
         
           
           
               
               
           
         
       
       wherein
 X is C(R 1 ) or N, in which R 1  is H, halo, or C 1 -C 10  alkyl; 
 R 3  is S—S—R a , S—R a , NO 2 , OR a , OC(O)R a , halo C 1 -C 10  alkyl, or aryl, in which R a  is C 1 -C 10  alkoxy, C 1 -C 10  alkyl, or C 1 -C 20  heterocycloalkyl and is optionally substituted with NRR′, halo, OR, C 3 -C 20  cycloalkyl, C 1 -C 20  heterocycloalkyl, aryl, or heteroaryl, each of R and R′, independently, being H or C 1 -C 10  alkyl; and 
 each of R 2 , R 4 , and R 5 , independently, is H, halo, or C 1 -C 10  alkyl; 
 provided that, when X is CH, R 3  is not OC(O)CH 3 . 
 
     
     
       2. The compound of  claim 1 , wherein R 3  is S—S—R a  or NO 2 , in which R a  is C 1 -C 10  alkyl optionally substituted with NRR′, each of R and R′, independently, being H or C 1 -C 10  alkyl. 
     
     
       3. The compound of  claim 2 , wherein R 3  is S—S—R a , in which R a  is CH 3  or CH 2 CH 2 N(CH 3 ) 2 . 
     
     
       4. The compound of  claim 3 , wherein X is C(R 1 ), in which R 1  is H or F. 
     
     
       5. The compound of  claim 4 , wherein each of R 2 , R 4 , and R 5  is H. 
     
     
       6. The compound of  claim 1 , wherein R 3  is halo C 1 -C 10  alkyl, or aryl. 
     
     
       7. The compound of  claim 6 , wherein R 3  is F methyl, isopropyl, or phenyl. 
     
     
       8. The compound of  claim 7 , wherein X is C(R 1 ), in which R 1  is H or F. 
     
     
       9. The compound of  claim 8 , wherein R 5  is H or F and each of R 2  and R 4  is H. 
     
     
       10. The compound of  claim 1 , wherein R 3  is OC(O)R a , in which R a  is C 1 -C 10  alkyl optionally substituted with halo, OR, C 3 -C 20  cycloalkyl, C 1 -C 20  heterocycloalkyl, aryl, or heteroaryl, R being H or C 1 -C 10  alkyl. 
     
     
       11. The compound of  claim 10 , wherein R 3  is OC(O)R a , in which R a  is methyl optionally substituted with Cl, Br, OCH 3 , or 
       
         
           
           
               
               
           
         
       
     
     
       12. The compound of  claim 11 , wherein X is C(R 1 ) or N, in which R 1  is H. 
     
     
       13. The compound of  claim 12 , wherein each of R 2 , R 4 , and R 5  is H. 
     
     
       14. The compound of  claim 1 , wherein the fluorophore comprises a naphthalene moiety, a cyanine moiety, an oxazine moiety, a coumarin moiety, a rhodamine moiety, or a xanthene moiety, each of which is optionally substituted with C 1 -C 10  alkyl, C 2 -C 10  alkenyl, C 2 -C 10  alkynyl, C 3 -C 20  cycloalkyl, C 3 -C 20  cycloalkenyl, C 1 -C 20  heterocycloalkyl, C 1 -C 20  heterocycloalkenyl, aryl, heteroaryl, OR b , SR b , NR b R c , COOR b , or COR b , each R b  and R c , independently, being H or C 1 -C 10  alkyl. 
     
     
       15. The compound of  claim 14 , wherein the fluorophore comprises a moiety selected from the group consisting of: 
       
         
           
           
               
               
           
         
         in which n is 1, 2, or 3, each of A and A′, independently, is a 5-7 membered ring optionally fused with at least one 5-7 membered ring, and each moiety is optionally substituted with C 1 -C 10  alkyl, C 2 -C 10  alkenyl, C 2 -C 10  alkynyl, C 3 -C 20  cycloalkyl, C 3 -C 20  cycloalkenyl, C 1 -C 20  heterocycloalkyl, C 1 -C 20  heterocycloalkenyl, aryl, heteroaryl, OR b , SR b , NR b R c , COOR b , or COR b , each R b  and R c , independently, being H or C 1 -C 10  alkyl. 
       
     
     
       16. The compound of  claim 15 , wherein the fluorophore is 
       
         
           
           
               
               
           
         
       
     
     
       17. An imaging method, comprising:
 delivering a compound of  claim 1  into a cell; and 
 irradiating the cell with an excitation light, thereby generating fluorescence from the cell. 
 
     
     
       18. The method of  claim 17 , wherein the fluorescence has a wavelength greater than about 600 nm. 
     
     
       19. A compound, comprising:
 a fluorophore covalently bonded to at least one protected sulfonate group of formula (I): 
 
       
         
           
           
               
               
           
         
       
       wherein
 X is C(R 1 ) or N, in which R 1  is H, halo, or C 1 -C 10  alkyl; 
 R 3  is H, S—S—R a , S—R a , NO 2 , OR a , OC(O)R a , halo, C 1 -C 10  alkyl, or aryl, in which R a  is C 1 -C 10  alkoxy, C 1 -C 10  alkyl, or C 1 -C 20  heterocycloalkyl and is optionally substituted with NRR′, halo, OR, C 3 -C 20  cycloalkyl, C 1 -C 20  heterocycloalkyl, aryl, or heteroaryl, each of R and R′, independently, being H or C 1 -C 10  alkyl; 
 each of R 2 , R 4 , and R 5 , independently, is H, halo, or C 1 -C 10  alkyl; and 
 the fluorophore comprises a cyanine moiety, an oxazine moiety, a coumarin moiety, a rhodamine moiety, or a xanthene moiety, each of which is optionally substituted with C 1 -C 10  alkyl, C 2 -C 10  alkenyl, C 2 -C 10  alkynyl, C 3 -C 20  cycloalkyl, C 3 -C 20  cycloalkenyl, C 1 -C 20  heterocycloalkyl, C 1 -C 20  heterocycloalkenyl, aryl, heteroaryl, OR b , SR b , NR b R c , COOR b , or COR b , each R b  and R c , independently, being H or C 1 -C 10  alkyl; 
 provided that, when X is CH, R 3  is not OC(O)CH 3 . 
 
     
     
       20. The compound of  claim 19 , wherein the fluorophore comprises a moiety selected from the group consisting of: 
       
         
           
           
               
               
           
         
         in which n is 1, 2, or 3, each of A and A′, independently, is a 5-7 membered ring optionally fused with at least one 5-7 membered ring, and each moiety is optionally substituted with C 1 -C 10  alkyl, C 2 -C 10  alkenyl, C 2 -C 10  alkynyl, C 3 -C 20  cycloalkyl, C 20  cycloalkenyl, C 1 -C 20  heterocycloalkyl, C 1 -C 20  heterocycloalkenyl, aryl, heteroaryl, OR b , SR b , NR b R c , COOR b , or COR b , each R b  and R c , independently, being H or C 1 -C 10  alkyl. 
       
     
     
       21. The compound of  claim 20 , wherein the fluorophore is 
       
         
           
           
               
               
           
         
       
     
     
       22. The compound of  claim 19 , wherein R 3  is H. 
     
     
       23. The compound of  claim 19 , wherein X is C(R 1 ), in which R 1  is H or F. 
     
     
       24. The compound of  claim 19 , wherein each of R 2 , R 4 , and R 5 , independently, is H or F.

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